Docetaxel (1, Taxotere) a semi-synthetic analog and paclitaxel (2, Taxol) a complex diterpene isolated from the bark of Taxus brefivolia are arguably the most outstanding cancer chemotherapeutic substances discovered in recent times. While paclitaxel can be obtained from the yew tree or semi-synthetically, only the latter option is currently available for the formation of non-natural docetaxel. The partial synthesis of this important compound has generally been accomplished through esterification of a derivative of the (2R, 3S) phenylisoserine side chain with a protected form of 10-deacetylbaccatin III, a comparatively abundant natural product also present in the yew tree.
In Colin's U.S. Pat. No. 4,814,470, it was reported that a taxol derivative, commonly referred to as taxotere, has an activity significantly greater than taxol.
Docetaxel and paclitaxel may be prepared semi-synthetically from 10-deacetylbaccatin III or baccatin III as set forth in U.S. Pat. Nos. 4,924,011 and 4,924,012 or by the reaction of a β-lactam and a suitably protected 10-deacetylbaccatin III or baccatin III derivative as set forth in U.S. Pat. No.5,175,315. 10-deacetylbaccatin III (10-DAB, 3) and Baccatin III (4) can be separated from mixtures extracted from natural sources such as the needles, stems, bark or heartwood of numerous Taxus species and have the following structures.

Most of the research towards the semi-synthesis of docetaxel and paclitaxel has involved 10-deacetylbaccatin III as the starting material. The conversion of 10-deacetylbaccatin III into either docetaxel or paclitaxel is typically achieved by protecting the hydroxy groups: at C-7 and C-10 positions (for docetaxel) and only C-7 position (for paclitaxel), attachment of an acetyl group at the C-10 position (for paclitaxel), attachment of a C-13 β-amido ester side chain at the C-13 position through esterification of the C-13 alcohol with the β-lactam moiety, and deprotecting at C-7 for paclitaxel and C-7, C-10 for docetaxel.
The research for the semi-synthesis of these two important (docetaxel and paclitaxel) chemotherapeutic agents has been from 10-deacetylbaccatin III because it is the major metabolite present in the European Yew (Taxus baccata). However, another abundant taxane, 9-dihydro-13-acetylbaccatin III (9DHB, 5) present in the Canadian Yew (Taxus Canadensis) can be utilized for the semi-synthesis of docetaxel and paclitaxel. The present invention demonstrates how to convert 9-dihydro-13-acetylbaccatin III into taxane intermediates: 10-deacetylbaccatin III, baccatin III, docetaxel and paclitaxel.
